Clinical and laboratory studies are conducted to determine the etiology (infection, immunity and/or genetics) of chronic diseases of the neuromuscular system and design effective therapies. Current studies involve patients with polymyositis, dermatomyositis, inclusion body myositis, post-polio syndrome, demyelinating polyneuropathies, neuromuscular diseases associated with HIV infection, metabolic myopathies, hypokalemic periodic paralysis, dystrophies, myastenia gravis, diabetic neuropathies and stiff-man syndrome. The pathogenesis of post-polio syndrome is explored with a series of electro- physiological, virological, immunological and histological studies. Persistent or mutant poliovirus is sought in these patient's tissues using tissue cultures, PCR, and in situ hybridization. The mechanism of post-polio fatigue, a common and disabling symptom in many patients, is examined by analysis of the neuroendocrine axis, Magnetic Resonance Spectroscopy and sleep studies. Sequence of the beta-amyloid presursor protein gene was performed in patients with familial and sporadic inclusion body myositis. The spectrum of neuromuscular disorders associated with HIV infection has been studied, and the role of the virus and induced cytokine in the cause of neuropathy or myopathy is investigated with a variety of immunocytochemical studies, in situ hybridization and PCR. The antiretroviral drug ddC was found to cause a unique neuropathy characterized by abnormal mitochondria as determined by various morphological, molecular and biochemical studies. The cytotoxic basis of anti-GAD antibodies in patients with stiff-man syndrome is investigated and changes in the antibody titers are studied in vivo and in vitro and during therapy. Randomized-controlled clinical trials are conducted using high-dose Intravenous immunoglobulin in patients with polymyositis, dermatomyositis, inclusion body myositis, chronic inflammatory and paraproteinemic demyelinating polyneuropathies, stiff-man syndrome, myasthenia gravis and diabetic autoimmune neuropathy. A controlled study using dichlorophenamide, a carbonic anhydrase inhibitor, has been conducted in patients with hypokalemic periodic paralysis. Another controlled study using L-carnitine has been also conducted in patients with AZT-induced mitochondrial myopathy with carnitine depletion.